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@ARTICLE{Brenner:283019,
      author       = {Brenner, Juliette and Bastiaansen, Anna E. M. and Guasp,
                      Mar and Muñiz-Castrillo, Sergio and Iizuka, Takahiro and de
                      Bruijn, Marienke A. A. M. and Muñoz-Lopetegi, Amaia and
                      Martínez-Hernández, Eugenia and Picard, Géraldine and
                      Vogrig, Alberto and Millot, Mathilde and Finke, Carsten and
                      Geis, Christian and Lewerenz, Jan and Melzer, Nico and
                      Prüss, Harald and Räuber, Saskia and Ringelstein, Marius
                      and Rostàsy, Kevin and Sühs, Kurt-Wolfram and Thaler,
                      Franziska S. and Wandinger, Klaus-Peter and Wurdack,
                      Katharina and Crijnen, Yvette S. and Kerstens, Jeroen and
                      van Steenhoven, Robin W. and Veenbergen, Sharon and
                      Schreurs, Marco W. J. and van den Berg, Robert and Volovici,
                      Victor and Neuteboom, Rinze F. and de Vries, Juna M. and
                      Sillevis Smitt, Peter A. E. and Nagtzaam, Mariska M. P. and
                      Franken, Suzanne C. and Ratuszny, Dominica and Menge, Til
                      and Bertolini, Annikki and Bien, Christian and Berger,
                      Robert and Tauber, Simone and Angstwurm, Klemens and
                      Seifert-Held, Thomas and Kraft, Andrea and Klausewitz,
                      Jaqueline and Ayzenberg, Ilya and Eisenhut, Katharina and
                      Roessling, Rosa and Heiden, Martha and Kümpfel, Tania and
                      Dalmau, Josep and Leypoldt, Frank and Honnorat, Jérôme and
                      Titulaer, Maarten J.},
      title        = {{D}evelopment and validation of the {NEOS}2 score for
                      prediction of long-term outcomes and improvement after
                      first-line immunotherapy in patients with anti-{NMDAR}
                      encephalitis: an international cohort study},
      journal      = {The lancet / Regional health. Europe},
      volume       = {62},
      issn         = {2666-7762},
      address      = {[Amsterdam]},
      publisher    = {Elsevier},
      reportid     = {DZNE-2025-01431},
      pages        = {101562},
      year         = {2026},
      note         = {Funding: This study was funded by Dioraphte (charity;
                      project 2001 0403).},
      abstract     = {Background: Anti-N-methyl-D-aspartate receptor (anti-NMDAR)
                      encephalitis is a severe disease that primarily affects
                      young people and can improve with adequate treatment. We
                      aimed to refine the anti-NMDAR Encephalitis One-year
                      functional Status (NEOS) score by developing NEOS2, an
                      updated model using readily available data at the time of
                      diagnosis. We assessed the predictive value of the
                      NEOS2-score for (1) improvement following first-line
                      treatment, (2) functional outcome at one-year follow-up, and
                      (3) resumption of school or work within three years.
                      Methods: In this international (France, Germany, Japan, the
                      Netherlands and Spain) cohort study in patients with a
                      definite anti-NMDAR encephalitis diagnosis (according to the
                      clinical criteria plus antibody testing in CSF), we
                      performed logistic regression analyses to develop and
                      validate multivariable models to predict -based upon
                      variables available at diagnosis- short (ΔmRS two weeks
                      after first-line treatment), middle (modified Rankin Scale
                      [mRS] at one year), and long-term (return to school or work
                      within three years) outcomes. We included clinical variables
                      and biomarkers available at diagnosis. Findings: We included
                      702 patients (mean age 23 years, $95\%-CI$ 2–69; $79\%$
                      female, $21\%$ male) diagnosed between the discovery of the
                      disease in 2007 and 2022. Most patients $(96\%;$ 672/702)
                      had received first-line immunotherapy, and $38\%$ (233/615)
                      showed improvement within two weeks. One year after
                      diagnosis, $80\%$ (517/644) had a favourable functional
                      outcome (mRS≤2). At three years, $73\%$ (203/278) had
                      resumed work/school. In multivariable analysis, higher age
                      (odds ratio [OR] 0·35, $95\%-CI$ 0·29–0·43, p <
                      0·0001), treatment delay (OR 0·49, $95\%-CI$
                      0·41–0·58, p < 0·0001), movement disorders (OR 0·32,
                      $95\%-CI$ 0·24–0·41, p < 0·0001), ICU-requirement (OR
                      0·34, $95\%-CI$ 0·26–0·44, p < 0·0001) and increased
                      CSF leucocyte count (OR 0·65, $95\%-CI$ 0·60–0·71, p <
                      0·0001) independently predicted poorer outcomes (NEOS2,
                      accuracy AUC $80\%,$ $95\%-CI$ $75–86\%).$ The same
                      variables, excluding age, were relevant in predicting
                      improvement following first-line immunotherapy (NEOS2-T AUC
                      $81–84\%,$ $95\%-CI$ $77–86\%).$ Return-to-work or
                      -school served as a useful measure of longer-term outcomes,
                      predicted with equal accuracy as one-year functional outcome
                      (NEOS2-W AUC $80\%,$ $95\%-CI$ $75–85\%).$ The
                      NEOS2-score, applied as an ordinal measure, enabled nuanced
                      predictions of outcome probabilities across the score
                      spectrum, ranging from a high $(80\%;$ n = 20/25) likelihood
                      of improving after first-line immunotherapy and achieving a
                      good outcome $(100\%;$ n = 32/32) to a high risk of
                      first-line treatment failure $(97\%;$ n = 77/79) and no
                      return to school/work $(94\%;$ n = 15/16). Interpretation:
                      The NEOS2-score, readily available at diagnosis and easy to
                      apply, can identify patients with either a favourable or
                      poor prognosis, and those who may benefit from early
                      intensified treatment. The value of the NEOS2-score for
                      guiding treatment decisions and as a stratification tool in
                      studies on optimal treatment regimens, should be confirmed
                      in further prospective studies.},
      cin          = {AG Prüß},
      ddc          = {610},
      cid          = {I:(DE-2719)1810003},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      doi          = {10.1016/j.lanepe.2025.101562},
      url          = {https://pub.dzne.de/record/283019},
}